Transition Metal Catalyzed Bond Formation Reactions On Saturated Carbon

Transition metal-catalyzed cross-coupling reactions which involving alkyl electrophiles, as directly concerned about the saturated carbon bond formation reaction, has emerged as an important method in modern organic synthesis. In chapter one, the history and current status of Ni catalyzed cross-coupling of alkyl electrophiles is summarized. After a brief update on the recent progress of copper, palladium, iron, cobalt catalyzed cross coupling reaction involving alkyl electrophilic reagent, we come to the the conclusion that although there have been numerous reports about transition metal-catalyzed coupling reactions with alkyl electrophiles and nucleophiles, but there are still many challenges. The reactions concerned about secondary alkyl electrophiles are still rare. The uncleophiles are limited to carbon atom. And the terminal alkynes can not react with the secondary electrophiles.For the problem of unclephiles is limited to carbon atom. In chapter two, we developed a novel use of boron as unclophile in alkyl Miyaura reaction. We reported the first Pd catalyzed primary alkyl Miyaura reaction. However, Pd could not achieve the borylation of secondary alkyl electrophiles. Then we reported the first Ni catalyzed secondary alkyl Miyaura reaction. Compared with the former report of Cu catalyzed borylation by our group, the Pd catalyzed reaction had better chemical selectivity, which only primary alkyl halide was reacted. The Ni catalyzed borylation had a distinct ligand effort compared with Cu. Fu group had developed a serie of Ni catalyzed asymmetric carbon-carbon bond-forming reactions by secondary alkyl electrophiles. Since the ligand was required, this gave us a unique opportunity to control the asymmetric of the carbon-boron bond. We also made some attempts to Ni catalyzed asymmetric carbon-boron bond formation. The Pd catalyzed borylation might involve an SN2mechanism and the Ni catalyzed borylation might involve a free radical mechanism.For the problem of terminal alkynes could not react with secondary alkyl electrophiles. In chapter three, we first reported the Ni catalyzed Sonogashira reactions with secondary electrophiles. A less hindered tridentate nitrogen ligand of Pybox was used to achieve a smooth coupling reaction of secondary alkyl electrophile with terminal alkyne. The new report avoided the use of alkyl metal reagents, alkynyl electrophiles or alkynyl metal reagents which were wildly used but were difficult to attach by the previous reports. The reaction had good diastereoselectivity of cyclic substituted alkyl electrophiles, and the products were mainly in a thermodynamically stable conformation. And we further evidenced by a single crystal. Some biologically active molecules could be conveniently further derivatized; the TMS-caped alkyne could achieve double alkylation. After preliminary studies into the mechanism, we believed that this reaction also experienced a radical mechanism. The tertiary alkyl electrophiles were also tested, but the main products were the dimeric oxidative coupling of alkynes. The tertiary alkyl electrophiles might play the role of oxidant.